In der vorliegenden Habilitationsschrift werden neue Aspekte der periazetabulären Osteotomie (PAO) zur Behandlung der Hüftdysplasie untersucht. Im Fokus stehen intraoperative Modifikationen, perioperative Maßnahmen und postoperative Ergebnisse.

Intraoperativ wurden alternative Fixationstechniken evaluiert, insbesondere die Stabilität der Schraubenfixation mit und ohne horizontale Schraube sowie einer schraubenlosen K-Draht-Fixation. Ziel war die Analyse von Fixationsstabilität, Komplikationsraten und klinischen Ergebnissen über einen 5-Jahres-Zeitraum.

Perioperativ wurde der Einsatz eines Regionalverfahren als schmerztherapeutische Maßnahme untersucht, um den intraoperativen Opioidverbrauch zu reduzieren.

Postoperativ standen die Rückkehr zum präoperativen Aktivitätsniveau, Anpassungen der sportlichen Aktivität sowie die Auswirkungen der PAO auf Schwangerschaft und Geburtsweg im Vordergrund. Die Ergebnisse sollen die Entscheidungsfindung für Patient:innen und Behandler:innen erleichtern und die Therapie der Hüftdysplasie optimieren.

Die häufigsten malignen Tumoren des Pankreas sind exokrine Pankreaskarzinome. Betroffene Patient:innen haben nach wie vor eine stark eingeschränkte Prognose und lediglich ein Bruchteil ist zum Zeitpunkt der Diagnosestellung operabel. Die operative Resektion stellt weiterhin die einzige kurative Therapiemöglichkeit dar. Auch nach erfolgreicher onkologischer Resektion bleibt die Prognose der betroffenen Patient:innen stark eingeschränkt. Innerhalb der Gruppe resektabler Pankreaskarzinome besteht jedoch eine prognostische Heterogenität. Im Rahmen multimodaler Therapiekonzepte bildet eine prognostische Risikostratifikation die Grundlage für die Wahl des geeigneten Therapiekonzeptes. Die Präzisierung dieser Risikostratifikation bildet somit eine potentielle Grundlage für eine exaktere Indikationsstellung des geeigneten Therapiekonzeptes. Im Kontext der stark eingeschränkten Prognose des exokrinen Pankreaskarzinoms und der Morbidität onkologischer Resektionen ist die exakte prognostische Risikostratifikation essenziel für die bestmögliche Behandlung betroffener Patient:innen. Ziel der vorliegenden Arbeit ist die Herausarbeitung von Merkmalen prognostischer Heterogenität sowie die Präzisierung ihrer Identifizierung und somit die Weiterentwicklung dieser prognostischen Risikostratifikation bei Patient:innen mit resektablem exokrinen Pankreaskarzinom.

Fluid-rock interaction is a fundamental process in the earth system, capable of altering the chemical and physical properties of wall rocks, which in turn significantly influences the large-scale exposure of fluid-altered rock, geophysical observations and hydrothermal ore deposits. Greisenization represents such a fluid-rock interaction characterized by the replacement of biotite + feldspar by quartz + white mica ± topaz ± fluorite, which links fluid-rock interaction to the ore formation, particularly facilitating significant enrichments in W, Sn, and Li. However, the factors controlling greisen variation and the fluid evolution are not well understood. In this dissertation, I integrate natural sample analysis and a reactive transport model to investigate the greisenization process. The results indicate that the initial fluid composition, particularly F concentration and pH value, governs the variation of greisen. Additionally, boiling may serve as a mechanism to introduce F-rich fluid. Further, fluorine content in topaz is a probe to the F concentration change of fluid. This thesis emphasizes a novel perspective on how F influences the process of greisenization from natural observations to numerical modeling, which further contributes to a better understanding of greisen-related ore formation and F-related processes.

The first scientific section presents work on the Zinnwald/Cínovec quartz-topaz greisen, a typical example of fluid-rock interactions involving F-rich fluids. A transect with a width of 12 cm from this deposit presents a sequence of quartz-topaz greisen and weakly altered rhyolite. Mass balance calculation for this transect indicates a net gain of F, Si, etc. during greisenization. Fluid inclusions evidence suggests that boiling occurred during or before greisenization. To explain the observation, I propose a two-stage greisenization model. Initially, fluid boiling induces the phase separation of HF-rich vapor and brine. The vapor reacts with feldspar and biotite to form quartz and topaz, while mineral replacement creates significant transient porosity, which is then filled by brine and later sealed by the precipitation of quartz and fluorite due to oversaturation. This study underscores that fluid boiling, which introduces F-rich fluids, is essential for the formation of quartz-topaz-rich greisen.

Observations on Zinnwald/Cínovec quartz-topaz greisen reveal that the process of boiling introduces the F-rich fluid. However, the evolution of fluid composition is equally crucial to the mobility of metals of interest (e.g., W, Sn). In this case, topaz, a key F-bearing phase in quartz-topaz greisen, can be used to trace the fluid evolution, especially in terms of F content. In the second scientific section, I performed measurements of Raman spectrometry on topaz crystals collected from different locations. The results reveal that the distances of Raman bands shifts around 155 and 562 cm⁻¹ correlate with F concentration by a linear correlation (y = 0.329x – 113.6, where y represents F concentration and x the distance of Raman bands shifts around 155 and 562 cm⁻¹). Two types of topazes from the Zinnwald/Cínovec greisen profile were recognized based on CL imaging. The systematic F concentration difference of 0.4 wt. % among these two types of greisen indicates the F content change in the fluid equilibrated with greisen. This approach provides a newly practical method to determine F concentration in topaz, which could be used to trace the temporal (and/or spatial) evolution of aqueous F content during greisenization.

The case study of Zinnwald/Cínovec quartz-topaz greisen offers valuable insights into the formation of quartz-topaz greisen. However, the factors controlling the variation between quartz-topaz and quartz-mica greisen are not well understood. Based on the natural sample study, the third section of this dissertation introduces a reactive transport model to constrain the parameters governing the development of distinct greisen assemblages. The infiltrating fluid with a lower pH value and lower F concentration result in the formation of greisen characterized by a sequence of quartz-topaz and quartz-mica. In contrast, acdic fluid enriched in F (>0.015 mol/kg), lead to mica-free greisen formation. Additionally, the results of the numerical modeling suggest that quartz-topaz greisen has a higher porosity (14 %) compared to quartz-mica greisen (8 %), allowing that larger fluid volumes to pass through quartz-topaz greisen. These findings enhance our understanding of greisen variation and fluid evolution, which are critical to studying greisen-related ore formation.

In conclusion, the comprehensive study emphasizes the significance of quartz-topaz greisen in greisen systems, particularly its F-rich environment, which provides potential for rare metal enrichment. By examining processes from the mineral to the bulk rock scale, this work demonstrates that F plays a critical role in greisen systems. The novel method of determining F concentration in topaz through Raman spectroscopy enables the precise measurement. Moreover, the reactive transport model offers detailed constraints on fluid evolution during greisenization, improving the understanding of both greisen formation and associated ore deposits, such as those of W, Nb, and Ta. This dissertation covers a wide spectrum of greisen, providing valuable insights into the greisenization process.

Intra-tumor heterogeneity describes the coexistence of multiple genetically distinct subclones within the tumor of a patient resulting from somatic evolution, clonal diversification, and selection. It is a main causal driver of therapy resistance in the clinic by already containing subclones that are resistant to therapy or by subclones acquiring resistance to therapy. Therefore, the understanding of intra-tumor heterogeneity and tumor development may lead to new approaches and targets for treatment. In this thesis, I developed a method for the integrated analysis of bulk and single-cell DNA sequencing data of core-binding factor acute myeloid leukemia patients, which is defined by the presence of a RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene. I generated a combined bulk and single-cell dataset of 9 core-binding factor acute myeloid leukemia patients with samples at diagnosis, complete remission and relapse. Using this method, I was able to reconstruct tumor development including somatic variants, somatic copy-number alterations and fusion genes from a single tumor sample and, if available, from merged diagnosis and relapse samples showing tumor evolution under the pressure of chemotherapy. I performed an in-depth analysis of small-scale and large-scale genomic alterations of leukemia patients and, moreover, demonstrate that my developed method can detect subclonal copy-number alterations with a higher resolution as compared to current methods.

Seasonal outbreaks of Influenza A virus (IAV) infections repeatedly challenge the immune system, which is in charge of controlling viral replication and facilitating clearance and subsequently recovery. T cells, which are part of the adaptive immune system, provide a highly specific response towards IAV during the acute infection phase that supports viral clearance. For that, activated effector T cells migrate from the lung-draining lymph nodes (drLN) to the side of infection, where they induce cell death of infected cells. Besides effector function in the lung, the follicular T helper cell subset provides help to B cells in drLN thereby supporting plasma cell differentiation and production of neutralizing antibodies. Furthermore, memory T cells reside long term in the body and serve as protection against re-infections. Although the T cell response is crucial for virus control, it has to be tightly regulated as T cell induced immunopathology and collateral tissue damage is disadvantageous. The protein T cell activation inhibitor, mitochondrial (TCAIM) was previously found to interfere with effector T cell differentiation and function. Yet, TCAIM overexpressing T cells were able to respond to activating stimuli by entering the proliferation cycle and reduced cytokine production. Thus, within the scope of this work, the question was addressed, if the degree of T cell activation and differentiation in TCAIM overexpressing mice is sufficient to facilitate viral clearance and to support establishment of a protective memory T cell pool. Furthermore, no in vivo data are available for TCAIM deficient T cells, but previous in vitro work showed an advantage in T cell activation under sub-optimal stimulation conditions. This raises the question, whether viral control is improved in TCAIM deficient mice. The here presented data show an impaired lung infiltration of TCAIM overexpressing T cells upon IAV infection, which is linked to the failure to modulate CD44 and CD62L receptor expression and upregu-lation of genes involved in migration and effector T cell differentiation. As a functional consequence cytokine production was diminished and viral clearance delayed. Nevertheless, TCAIM overexpressing mice did recover from IAV infection and were able to respond to infection induced activation stimuli seen in undisturbed type I interferon (IFN) signalling and T cell expansion within drLN. Importantly, reduced T cell response at the side of infection prevented T cell induced immunopathology since TCAIM overexpressing mice only slightly lost weight. Surprisingly, although generation of lung homing effector and tissue resident memory T cells was impaired, neutralizing antibodies were formed which might serve as protection during re-infection. TCAIM deficient T cells were found to predominantly accumulate at the side of infection. Early upregulation of Ifng and genes involved in T cell activation however did not translate into increased IFN-γ production at the peak of infection and improved viral control. VI In conclusion, the data within this work highlight the impact of TCAIM on T cell migration and the prevention of T cell induced immunopathology thereby proposing a beneficial role during IAV infections.

The field of highly frustrated magnetism harbors a wide variety of exotic phases that sustain interest in the field with no end in sight. Competing interactions yield models that often remain highly fluctuating down to zero temperature, have long-range entangled ground states, or exhibit fractionalized excitations. The study of these frustrated models presents a challenge for experimental and theoretical methods alike, driving their development in the process. As a contribution to the field, this thesis both further develops the pseudo-fermion functional renormalization group and applies the method in collaborative studies involving complementary methods to reveal low-temperature properties of a selection of frustrated spin models with relevance to spin compound families of recent interest.

In the first chapters of the thesis, the pseudo-fermion functional renormalization group is extended to enable the treatment of spin models with broken time-reversal symmetry. Newly accessible applications include models with finite magnetic fields in the form of site-dependent Zeeman terms. While previous formulations of the method could investigate magnetically ordered models only in their paramagnetic regime, often achieved by a finite renormalization group parameter in the model, the new scheme further allows the study of magnetic phases in absence of this parameter. In an exploratory study across a selection of Heisenberg and XXZ models, magnetic order parameters and magnetization plateaus will be compared with literature results to reveal for which newly accessible applications the method is best suited.

In addition to method development, a major emphasis of the thesis is placed on the study of nearest-neighbor spin models on the pyrochlore lattice. It is argued that the S = 1/2 and S = 1 Heisenberg models assume nematic ground states that break either only C3, or both C3 and lattice inversion symmetry. Quantum and classical phase diagrams of the model with Heisenberg and Dzyaloshinskii-Moriya interactions, and of non-Kramers pyrochlores are computed as well. In this context, an in-depth study of the so-called Γ5 phase will resolve subtle order-by-disorder selections from quantum or thermal fluctuations at both zero and critical temperatures. Furthermore, a model contained in both phase diagrams will be presented that exhibits a temperature-dependent spin liquid to spin liquid transition driven by entropic selections between ground state submanifolds in the case of classical spins. While the intermediate-temperature spin liquid can be described by coexisting vector and matrix gauge fields, spin degrees of freedom associated with the matrix gauge field depopulate as the temperature is lowered, realizing a spin-ice phase in the process. Emphasis is put on the study of the corresponding quantum model and its vicinity in the phase diagrams. This model is found to be best described in analogy to the intermediate-temperature classical spin liquid.

In the last part of the thesis, the pseudo-fermion functional renormalization group is applied in collaboration with classical Monte Carlo and inelastic neutron scattering to resolve the low-temperature behavior and magnetic order of the three-dimensional tetra-trillium compound and spin liquid candidate K2Ni2(SO4)3. The phase diagram of a Heisenberg model on the tetra-trillium lattice contextualizes the strongly fluctuating behavior of K2Ni2(SO4)3 by hosting a large paramagnetic region close to the density functional theory model of K2Ni2(SO4)3. In a broader scope, this region establishes compounds of the langbeinite family, which are described by Heisenberg models on the tetra-trillium lattice, as a promising platform in the future search for three-dimensional quantum spin-liquid phases.

Universal quantum computing is a coveted goal in the current technological landscape. This thesis presents a theoretical study of qubit arrays, the basic system for processing quantum information, tackling three important problems using results from Lie groups and algebras. Since every real system is subject to decoherence, it is crucial to find quantum devices capable of fast dynamics. The quantum speed limit of a system serves as a measure of the minimum time in which a given unitary evolution can be performed, depending on its controls and qubit couplings. A new method for its estimation is introduced in this thesis. Furthermore, the estimator is extended to determine the quantum speed limit of state-to-state transfers and quantum gates acting on a logical subspace of the total Hilbert space. The number and type of controls and qubit couplings in the system also determine whether all operations in the system are feasible, i.e. whether the system is controllable. Controllability is a necessary property for universality. The thesis presents two controllability tests, which are particularly tailored to the case of qubit arrays: A classical test based on notions from graph theory and a hybrid quantum-classical algorithm that employs parametric quantum circuits. These tests greatly expand the number of cases that can be studied. Finally, a method for designing arbitrarily large controllable qubit arrays is presented. This is achieved by juxtaposing smaller controllable arrays and connecting them via tunable couplings. The modular architecture allows the construction of larger devices that are in principle suitable for universal quantum computing, even if the controllability of the overall system cannot be directly determined by previous tests. The concepts shown here introduce an arsenal of tools that can provide valuable information for the study and development of systems with the aim of bringing quantum technologies closer to universal quantum computing.

Repetitive negative thinking (RNT) is a problematic thinking style that encompasses rumination and worry. RNT is characterized by continuously dwelling on negative content, such as problems or unpleasant experiences. RNT is associated with negative affect and various psychopathological symptoms, and it even predicts the onset of these symptoms, making it a transdiagnostic risk factor for psychopathology. This qualifies RNT as an ideal candidate for interventions because its reduction can help avoid worsened affect and symptoms, and may even prevent psychopathology. Mindfulness interventions are promising to reduce RNT because mindfulness teaches us to become aware of experiences (e.g., thoughts and feelings) and approach these experiences in an observing and non-judgmental way instead of getting stuck in negativity. Previous findings suggest that mindfulness interventions may indeed be helpful to reduce RNT and symptoms, and to improve affect. However, it remains largely unanswered whether brief mindfulness interventions in daily life lead to immediate benefits for RNT and affect. Two randomized controlled trials were conducted as part of this dissertation to answer this question. In both studies, participants completed brief audio-guided mindfulness interventions multiple times per day over several days. Immediately after each intervention, participants reported their RNT and affect via experience sampling method (ESM). STUDY 1 investigated the effects of a mindfulness intervention in N = 91 non-clinical participants. Over 10 days, participants were randomized at each assessment to complete either a mindfulness intervention or an active control task consisting of listening to neutral background sounds. Results of STUDY 1 showed that participants reported less RNT and less negative affect after completing the mindfulness intervention as compared to the control condition. However, the associations between RNT and negative affect were not impacted by the mindfulness intervention. STUDY 2 investigated the effects of a detached mindfulness intervention in N = 100 participants with elevated trait RNT. The study consisted of a 5-day baseline phase with only ESM assessments and a 5-day intervention phase, where participants additionally engaged in either a detached mindfulness or an active control task, depending on which group they were randomized to. The control task was matched to the mindfulness intervention except for the mindfulness instructions and corresponded to a guided imagery task. Results of STUDY 2 showed that participants of both groups reported stronger reductions in RNT and in negative affect, and stronger improvements in positive affect during the intervention phase compared to the non-intervention baseline phase. However, there were no differences between the groups. The integration of the studies’ findings allows to draw conclusions about the effectiveness of mindfulness interventions and about the mechanisms causing benefits. Effectiveness. Findings suggest that detecting an effect of the mindfulness interventions depended on the control condition used as a comparison. Our guided mindfulness interventions led to less RNT and negative affect compared to both (i) not engaging in any task (STUDY 2) and (ii) listening to neutral background sounds (STUDY 1). However, the mindfulness intervention was equally effective as a matched control task that excluded mindfulness instructions (i.e., guided imagery; STUDY 2). Mechanisms. The studies of this dissertation do not allow us to conclusively determine which mechanisms caused the benefits across both mindfulness interventions and the guided imagery task. It could be that experiencing momentary mindfulness led to lower RNT and better affect. However, other mindfulness-unspecific mechanisms, such as expectations about the helpfulness of the tasks or distraction from current RNT and affect, may also have been (partly) responsible for the observed benefits. Overall, findings of this dissertation indicate that brief guided mindfulness interventions and guided imagery tasks are helpful to immediately reduce RNT and improve affect in daily life. Whether these tasks caused benefits by increasing momentary mindfulness or via other mechanisms remains to be elucidated.

The steady increase in urbanization presents several challenges for humans, as they are forced to adapt to an environment that differs from the natural habitats in which they evolved. Consequently, studying the effects of this environmental shift on psychological well-being has become increasingly important. Especially the influences of environmental sounds seem understudied. Previous research has demonstrated that exposure to natural sounds can improve cognitive performance and positive affect while exposure to urban sounds was found to be detrimental. In order to facilitate the benefits of natural sound exposure, a deeper understanding of the underlying psychological and neural mechanisms is essential. The current dissertation sought to provide insights into these mechanisms by investigating the brain’s response to environmental sounds via magnetic resonance imaging (MRI) and sub-clinical assessment of mental well-being. In Paper I (Stobbe et al., 2023), the impact of exposure to natural versus urban soundscapes on brain activity during cognitive performance was assessed. It was found that performance gains in a working memory task were associated with a reduction of activity in the medial prefrontal cortex (mPFC) proposing facilitated information processing in a subregion of the frontal executive network following exposure to a natural soundscape. Moreover, the reduction of negative emotions was linked to reduced activity in the inferior parietal lobule (IPL), a region that is part of the cognitive control network, suggesting that cognitive processes required less effort and elicited fewer negative emotions following the exposure to the natural soundscape condition. In Paper II (Stobbe et al., 2024), the effects of natural versus urban sounds on brain entropy (BEN) and functional connectivity (FC) during the sound exposure was examined. It was demonstrated, that the brain’s signal complexity, or BEN, in the posterior cingulate cortex (PCC) was significantly higher while participants listened to the urban soundscape. The increased BEN was found to be associated with a reduction of positive emotions in the urban soundscape condition, suggesting that the dislike of urban sounds might be represented by high signal complexity within the PCC. Additionally, it was discovered that FC in the auditory brain network was greater during exposure to natural soundscape compared to urban soundscape. This increment of FC was found to be associated with a performance gain on two working memory tasks, indicating that exposure to natural sounds could facilitate the brain’s processing efficiency via increased FC within a task relevant network. xii In Paper III (Stobbe et al., 2022), the influence of birdsongs versus traffic noise on depressive, anxious and paranoid states was investigated. It was found that while traffic noise exposure heightened the depressive states of healthy participants, exposure to birdsongs alleviated anxious and paranoid states in the same sample. These results suggest a possible explanation for the high prevalence of mental illness in urban areas while they simultaneously provide insights into how natural sounds such as birdsong could potentially be utilized to prevent the emergence mental illness. In conclusion, the present dissertation complements the debate on whether exposure to natural sounds can lead to improvements with respect to cognition and mental well-being and provides insights into possible mechanisms that underlie these benefits. These insights could contribute to more effective natural sound interventions and highlight the potential hazards of urban noise pollution.

The Baikal Archaeology Project (BAP: https://baikalproject.artsrn.ualberta.ca/) is a long-term, multidisciplinary research initiative that has brought together experts from the fields of archaeology, bioarchaeology, ethnoarchaeology, genetics, bio- and geochemistry, and palaeoecology for over two decades to explore the lifeways of prehistoric hunter-gatherer cultures in Northern Eurasia. The focus of the project is on investigating the cultural diversity, change, stability, and resilience of foraging cultures in response to changing environmental conditions in the Lake Baikal Region (LBR) in southern Siberia and the Lake Onega Region (LOR) in Karelia, eastern Fennoscandia. High-resolution continuous sediment sequences from lakes and peatbogs serve as valuable environmental archives, ideally suited for detailed reconstructions of past human-environment relationships in the respective study areas. This dissertation presents robustly dated, high-resolution palynological records and pollen-based biome reconstructions from both BAP regions, providing detailed insights into the climatic and environmental histories and how they may have influenced the hunter-gatherer cultures studied within the BAP. A pollen record from a 135-cm-long, radiocarbon-dated sediment core from Lake Kamenistoe (67°30'31.4" N, 34°38'53.3" E) provides important insights into the vegetation and climate dynamics of the central Kola Peninsula over the last ca. 13 ka BP. The results improve existing reconstructions of the retreat of the Scandinavian Ice Sheet at the end of the last glacial period, indicating that the region was already ice-free by 13 ka BP. The palaeoenvironmental record, integrated with existing archaeological data, suggests that the initial spread of early Mesolithic hunter-gatherer groups into the region took place no later than 10 ka BP and coincided with the expansion of the boreal forest and a phase of continuous warming. These changes likely prompted the northward migration of reindeer, which were a crucial resource for Mesolithic hunter-gatherers, facilitating the habitation of this region. The palaeoenvironmental study in the LOR is based on an 885-cm-long sediment core from Razlomnoe Peat (62°27'53" N, 34°26'4" E), composed of continuous deposits from the last ca. 11.8 ka BP. The results of the palynological analysis allowed detailed reconstruction of Lateglacial–Holocene environmental changes and their possible impacts on hunter-gatherer societies in the region. The findings show rapid postglacial afforestation and highlight the sensitivity of the regional vegetation to climatic changes, such as during the 8.2 ka BP and 4.2 ka BP events, which mark the beginning of the Middle and Late Holocene, respectively. The 8.2 ka BP event is characterised by a substantial spread of birch at the expense of pine, indicating markedly cooler winters and an increase in wildfire frequency. These abrupt changes coincide with the peak of use of the Yuzhniy Oleniy Ostrov burial ground (ca. 8250–8000 a BP), suggesting an adaptive response of hunter-gatherer communities to less favourable environmental conditions. The 4.2 ka BP event, often associated with drought in other regions, coincides in the LOR with wetter conditions, which led to the expansion of wetlands and the opening of the landscape. In a third study, records of pollen and microscopic charcoal particles from sediment cores from Lake Ochaul (54°13’58.4” N, 106°27’53.8” E) in Cis-Baikal and Lake Kotokel (52°47’ N, 108°07’ E) in Trans-Baikal were analysed to reconstruct and compare the vegetation and fire history of the last 32 ka BP in the two regions. In addition to information about the complex relationship between climate, vegetation, and fire activity, these records, in combination with archaeological data, also provide new insights into the activities of hunter-gatherer communities and their impact on the natural environment. Under the cold and dry conditions during the peak (32–18.2 ka BP) of the last glacial period, both records show minimal fire activity, likely due to sparse vegetation cover. The onset of deglaciation around 18.2 ka BP is marked by a gradual spread of woody plants, accompanied by a slight increase in fire activity. Significant differences in the fire records between the two study regions become evident at the end of the Lateglacial. The peak in fire activity in Cis-Baikal is dated to the Early Holocene (9.5–8 ka BP), while in Trans-Baikal, the peak occurred during the Middle Holocene (6–5 ka BP). These differences are likely primarily due to variations in vegetation composition and landscape openness. Charcoal concentrations in both sediment cores show low values during the so-called “cultural hiatus” in the Middle Neolithic (ca. 6660–6060 a BP), suggesting a population decline throughout the LBR. The spread of Late Bronze and Iron Age cultures from 3.5 ka BP onwards is likely related to the recorded increase in fire frequency around Lake Kotokel.

The AHR is a ligand dependent transcription factor, which belongs to the bHLH-PAS superfamily of proteins. Originally, the AHR was discovered for mediating the toxicity of environmental toxicants like TCDD and different PAHs. Advanced research showed that the AHR can be bound and activated by a wide range of agonists, including various exogenous and endogenous compounds. According to the classical description of the AHR pathway, the AHR is mainly located in the cytoplasm prior to ligandbinding. Most ligands own hydrophobic characteristics allowing them to enter the cell via diffusion.Ligand-binding to the AHR triggers a nuclear import followed by building a dimer with a protein called ARNT. This heterodimer recruits many co-factors, thereby getting access and subsequently binding to a special sequence in the DNA, the XRE. The AHR/ARNT complex bound to XRE induces the expression of xenobiotic metabolizing enzymes, including phase I and phase II enzymes, thus pointing to a key role of the AHR in xenobiotic metabolism. Examining the intracellular distribution of the AHR in living cells reveals that the AHR undergoes a shuttling between cytoplasm and nucleus. This shuttling occurs continuously and does not lead to any activation. Despite the huge number of studies examining the AHR, the localization remains scarcely investigated. In this thesis, the localization of the AHR was investigated thoroughly after transient transfection of EYFP-AHR leading to expression of a fluorescent fusion protein that can be detected in real-time in living cells. I validated this system by comparing the localization of the overexpressed AHR fusion protein with the endogenous AHR with and without the presence of ligands. First of all, in depth mutagenesis analyses on the crucial amino acids to dimerize with ARNT and bind to XRE were carried out. This aimed to characterize if these two significant steps might have an impact on maintaining the activated AHR in the nucleus after ligand-binding or generally affect its nucelo-cytoplasmic translocation in the basal state. Later, the regulatory motive responsible for intracellular distribution and nuclear import, namely NLS, was characterized using point mutations. Thereby, the intracellular distribution of the AHR variants that carry an impaired NLS was detected in the basal state or after ligand treatment. My results demonstrated that neither ARNT dimerization nor DNA binding have an impact on stabilizing the AHR in the nucleus prior or post ligand-binding. Moreover, the sequence of NLS was identified as (13RKRRK17) and (37KR-R40), whereby the first part represents the main regulator, while the second one has only a supportive and complementary role. Besides that, I examined both nuclear import processes of the AHR: basal and ligand-induced. Thereafter, the effect of novel import inhibitors IPZ and IVM was tested on the mentioned nuclear import of the AHR. I found that ligand induced import can occur when the basal import is diminished. At the same time, trying to block the nuclear import using import inhibitors showed comparable influence on both import pathways. My results proposed that ligand-induced and basal import happen autonomously and independent of each other, but they rely on the same particular mechanism. Taken together, this thesis expressed novel findings on the AHR’s sequence and the molecular components involved in its nucleo-cytoplasmic translocation using advanced methods.

Saponins are secondary metabolites that aid in plants’ defense against herbivory and have been used in ancient medical practices. Ginsenosides from Panax ginseng C.A.MEY, Curcumin from Curcuma longa L. and many more were explored for their anti-inflammatory, anti-cancer, and anti-fungal properties. Especially triterpenoid saponins like ginsenosides are well characterized whereas steroidal saponins like DT-13 are not well explored. Therefore, in this study we investigated the mechanism and targets of DT-13 as an anti-inflammatory compound. To achieve this, lipopolysaccharide (LPS) stimulated RAW264.7 mouse macrophages were used as in vitro inflammatory model. Cells pretreated with DT-13 were compared with those pretreated with Rk1 (ginseng saponin) and dexamethasone (synthetic anti-inflammatory drug). DT-13 inhibited pro-inflammatory cytokines more efficiently when compared to Rk1 and dexamethasone. DT-13 downregulated gene expression of tumor necrosis factor-alpha (TNFα), cyclooxygenases-2 (COX-2) by 85% and 99% respectively. It also inhibited interleukin-6 (IL-6) release from cells by 89% as measured by enzyme linked immunosorbent assay (ELISA). Like Rk1 and dexamethasone, DT-13 inhibited nuclear localization of phosphorylated-nuclear factor kappa B (p-NFκB), as observed with immunofluorescence microscopy. These results indicate that DT-13 acts as anti-inflammatory agent via NFκB signaling pathway. The confirmation of interference of NFκB signaling by DT-13 lead to investigation of other genes regulated by NFκB activation. Interestingly, it was observed that DT-13 reduced the expression of nod like receptor family pyrin binding domain 3 (NLRP3) and interleukin 1 beta (IL-1β) gene by 73% and 92% respectively. It also significantly inhibited NLRP3-inflammasome induced Caspase-1 activation and IL-1β release. Membrane attack complex formation was also inhibited as checked by alternate pathway (AP) complement assay. This concludes that it is involved in attenuation of NLRP3 inflammasome formation as well. It is known that ligand activated peroxisome proliferator activated receptor inhibits LPS stimulated NFκB gene activation by a mechanism called as ‘trans-repression’. DT-13 and Rk1 were explored as ligands for PPARγ activation using HEK transfection model system. DT-13 and Rk1 both significantly induced the expression of luciferase conjugated PPARγ response elements and hence the activation of PPARγ. This was also concluded by in silico study that shows the binding affinity of DT-13 in PPARγ ligand binding pocket similar to that of rosiglitazone. To summarise, all the results successfully concluded anti-inflammatory and anti-inflammasome properties of DT-13 via ligand activation of PPARγ in mouse macrophages.

Das akute Lungenversagen des Erwachsenen (acute respiratory distress sydnrome, ARDS) hat trotz über 50jähriger Erforschung eine anhaltend hohe Mortalität.

Die in dieser Habilitationsschrift vorgestellten Arbeiten untersuchten spezifische Fragestellungen zur Organdysfunktion und Anwendung extrakorporaler Organersatzverfahren im ARDS durch Anpassung bestehender experimenteller Modelle.

Nach Etablierung eines Modells prolongierter stabiler gemischter Azidämie und Hypoxämie ohne Induktion einer weiteren Pathologie gelang der experimentelle Nachweis, dass selbst eine kurzzeitige Exposition gegenüber einer Azidämie von nur wenigen Stunden in histologisch nachweisbaren Nierenschäden resultieren kann. Die zusätzliche Exposition gegenüber einer Hypoxämie verstärkte die beobachteten zellulären Schäden. Der Einfluss einer mögliche Inflammationsreaktion auf die Induktion der Azidämie wurde dabei durch u.a. umfangreiche immunhistochemische Analysen der Nieren bestmöglich ausgeschlossen. Die Ergebnisse der Experimente unterstützen die Hypothese, dass energieaufwendige renale Mechanismen der Protonenexkretion ursächlich für die Nierenschäden waren und wahrscheinlich zumindest ein Teil der komplexen Pathogenese des akuten Nierenversagens von kritisch Erkrankten darstellen.

Die Anpassung des Surfactantdepletionsmodells ermöglichte die Untersuchung der Validität thermodilutionsbasierter Messungen des Herzzeitvolumens während der Anwendung einer veno-venösen extrakoroporalen Membranoxygenierung (V-V ECMO). Die Ergebnisse demonstrierten zusammengefasst, dass thermodilutionsbasierte Messungen des HZV während einer V-V ECMO-Therapie nicht valide sind und um mehrere Liter pro Minute vom aortal gemessenen HZV abweichen können. Die Größe des Fehlers nahm dabei mit der Höhe der Rezirkulationsfraktion des extrakorporalen Blutflusses zu.

Auf Grund der steigenden Zahl mit ECMO therapierter ARDS-Erkrankter während der Covid-19 Pandemie untersuchte die letzte Arbeit der Habilitationsschrift den Zusammenhang zwischen der ECMO-Therapiedauer und dem intensivstationären Überleben von ARDS-Erkrankten mit Covid-19-Pneumonie. Die vorläufig ausgewerteten Daten einer laufenden Observationsstudie legten dabei nahe, dass ARDS-Erkrankte mit Covid-19-Pneumonie eine deutlich längere Unterstützung mit einer V-V ECMO benötigten als ARDS-Erkrankte, die das Lungenversagen auf Grundlage einer anderen Ätiologie erworben hatten, um von der ECMO-Behandlung zu profitieren.

Die Myasthenia gravis (MG) ist die häufigste neuromuskuläre Autoimmunerkrankung, die antikörpervermittelt zu einer Störung der neuromuskulären Übertragung und klinisch zu einer belastungsabhängigen Muskelschwäche führt. Mit dem Einzug moderner Therapieoptionen eröffnen sich viele neue therapeutische Optionen für die MG. Eine verbesserte Behandlung der MG-Patient*innen ist dringend notwendig, da deren Lebensqualität und Teilhabe am Leben gerade auch im langfristigen Verlauf erheblich eingeschränkt ist. Aktuell Fehlen prädiktive Biomarkern, die nicht nur den Erkrankungsverlauf, sondern auch das individuelle Ansprechen auf die verschiedenen Therapien vorhersagen können. Im Rahmen dieser Habilitationsschrift sind die Ergebnisse meiner bisherigen Arbeiten zur Analyse von klinischen Risikofaktoren für einen schlechten MG-Verlauf sowie Biomarker-Studien zur Erfassung der Erkrankungsaktivität und möglichen Therapie-Ansprechens zusammenfassend dargelegt, welche das Ziel haben einer individualisierten Patientenversorgung näher zu kommen. Dabei konnte als klinischer Risikofaktor für einen hochaktiven Erkrankungsverlauf im Sinne der Prädiktion einer myasthenen Krise, die Erkrankungsschwere zum Diagnosezeitpunkt festgestellt werden. Mit Hilfe der Daten des Deutschen Myasthenie- Registers konnten wir zu Beginn der COVID-19 Pandemie zeigen, dass MG-Patient*innen mit einer COVID-19-Infektion und bestehender immunsuppressiver Therapie ein schlechteres Outcome gemessen an der Rate der Hospitalisation und insbesondere eine höhere, krankheitsspezifische Letalität im Vergleich zu anderen Autoimmunerkrankungen aufweisen. In Bezug auf mögliche Biomarker konnten drei Kandidaten detektiert werden: Serum Calprotectin ist ein etablierter Marker der mikrobiellen Dysbiose und korreliert mit der klinisch aktiven MG. Dieser Marker könnte daher helfen neben den klinischen Skalen, die Krankheitsaktivität zu bestimmen. Darüber hinaus unterstreicht diese Studie die pathophysiologische Bedeutung der Darm-Dysbiose für die MG und bietet die Grundlage zur weiteren Erforschung möglicher neuer modulierender Therapien des Darmmikrobioms. Serum Neurofilament light chain ist insbesondere bei der Acetylcholinrezeptor-(AChR)-Ak positiven MG deutlich erhöht und könnte als prognostischer Marker, v.a. bei hochaktiven Verläufen unter intensivierter Therapie eingesetzt werden, um eine irreversible Destruktion an der neuromuskulären Endplatte zu vermeiden. Komplementaktivierungsmarker sind bei der AChR-Ak positiven MG erhöht und sinken unter immunsuppressiver Therapie. Die Messung der Komplementaktivierung könnte daher ein möglicher prädiktiver Biomarker zur Detektion des therapeutischen Ansprechens für die AChR-Ak positiven MG darstellen.

The present thesis provides an in-depth study of the barrier function of the skin by investigating the penetration of two toxicologically important substance classes: polycyclic aromatic hydrocarbons (PAH) and the metal allergens nickel, cobalt and palladium. Furthermore, the method of tape stripping was scrutinized to reveal the removal rate of stratum corneum (s.c.) with each tape strip. Skin contact to harmful substances can occur through consumer products containing them. Harmful substances are added to consumer products either by design — for example, as additives in plastic or certain metals in alloys — or inadvertently as contaminants. PAH were found to contaminate those plastics that are dyed with carbon black or contain mineral oils used as plasticizers. Nickel, cobalt and palladium, known to cause allergic contact dermatitis, are added into alloys in jewelry to attain certain characteristics such as color or corrosion resistance.

Skin penetration studies rely on the well-established in vitro Franz diffusion cell (FDC) assay. A skin sample or model is fixed over a receptor chamber containing an aqueous medium. The substance of interest is applied onto the skin in a matrix, for example, in solvents, petrolatumor in the consumer products themselves. After a certain incubation time, the compartments are analyzed to reveal the penetration rates of that substance into the skin.

In order to quantify the amount of substance in separate s.c. layers, the technique of tape stripping plays an important role. A tape strip is pressed onto the skin and removes a layer of the s.c. when taken off. However, the amount of s.c. removed with each tape strip is still subject of scientific debate. In a histological study presented here, the s.c. was removed by tape stripping of pigskin and the remaining s.c. was quantified microscopically. The study revealed a linear decrease in s.c. in terms of thickness as well as number of cell layers up to 20 removed tape strips. Each tape strip removed about one cell layer, corresponding to 0.4 μm.

In this thesis, the penetration of PAH through the s.c. was extensively studied. The influence of lipophilicity — expressed by the octanol-water partition coefficient (logP) — on the permeability of these toxic compoundswas demonstrated. Applying 24 different PAH(152–302 g/mol, logP: 3.9–7.3) in acetonitrile in an FDC assa, revealed that more lipophilic PAH exhibit lower penetration rates. Furthermore, the penetration was investigated for time intervals ranging from 2 h to 48 h. Highly lipophilic, six-ringed PAH like the dibenzopyrenes did not permeate the skin at all, whereas the less lipophilic, three-ringed PAH like acenaphthene permeate after 2 h already. The evaluation of FDC assays using human and pigskin allowed for the comparison of these two skin types. Human s.c. was shown to retain a greater share of the PAH that partition into the skin than porcine s.c.

The dependence on lipophilicity of PAH skin penetration is further supported by experiments that aimed to determine partition and diffusion coefficients of five selected PAH from a polypropylene surrogate (squalane) into porcine s.c. The PAH content in the skin compartments was quantified by gas chromatography coupled to tandem mass spectrometry. The use of tape stripping resulted in a concentration profile along the s.c. This profile was fitted to a solution of Fick’s second law, allowing the calculation of partition and diffusion coefficients. The partition coefficients positively correlated with the logP, while the diffusion coefficient was highest for naphthalene and about the same for the other PAH.

Nickel and cobalt are, contrary to palladium, part of the standard patch test used as diagnostic tool to detect contact allergies. Therefore, fewer allergies against palladium are diagnosed than those against nickel and cobalt. Nonetheless, Pd2+ exhibited higher frequencies of CD154+ in an in vitro activated marker assay in human blood samples thanNi2+ and Co2+. A reason for the lower number of diagnosed palladium allergies next to fewer tests could be a lower penetration rate of Pd2+ as compared to Ni2+ or Co2+. To test this hypothesis, FDC assays using pigskin were employed. Patch test preparations used for clinical diagnosis (the respective metal salt dispersed in petrolatum) were given onto the skin and incubated for 48 h, which corresponds to the time frame of a patch test. Additionally, FDC assays with the three ions in an aqueous solution were carried out to evaluate penetration rates independent of ion solubility. The recoveries in the skin compartments were quantified by inductively coupled plasma mass spectrometry. Pd2+ showed lower penetration rates than Ni2+ and Co2+, regardless of application in petrolatum or aqueous solution, thus confirming the hypothesis.

Collectively, these studies contribute to the understanding and analysis of the s.c. barrier function and the factors influencing the dermal penetration of two distinct classes of toxicologically relevant substances.

Überlebende kritischer Erkrankung zeigen häufig auch Jahre nach Entlassung von der Intensivstation (ITS) funktionelle Beeinträchtigungen. Diese Beeinträchtigungen betreffen die kognitiven Funktionen, die mentale Gesundheit und die körperlichen Funktionen. Sie werden als Post-Intensive Care Syndrom (PICS) zusammengefasst und beeinträchtigen die gesundheitsbezogene Lebensqualität. Der erste Teil dieser Habilitationsschrift beschäftigt sich mit der Detektion von Patient*innen mit PICS. Es wurde zunächst gezeigt, dass sich zwei kurze Items zur Einschätzung der subjektiven mentalen und körperlichen Gesundheit eignen, um die gesundheitsbezogene Lebensqualität von ITS-Überlebenden einzuschätzen. Durch die Kürze der Items können diese auch sehr gut im ambulanten und hausärztlichen Bereich eingesetzt werden. Diese Items können auch genutzt werden, um eine Veränderung der subjektiven Gesundheit im Vergleich zum Status vor der ITS-Aufnahme festzustellen. Patient*innen mit PICS lassen sich nicht nur durch individuelle Untersuchungen, sondern auch anhand von Routinedaten identifizieren. Aus Routinedaten der Krankenhäuser können beispielsweise Patient*innen mit einer langfristigen Abhängigkeit vom Respirator identifiziert und charakterisiert werden. Der zweite Teil dieser Habilitation beschäftigt sich mit Maßnahmen, um die Qualität der ITS-Behandlung zu steigern und damit Risikofaktoren für die Entstehung eines PICS zu reduzieren. Care-Bundles auf der ITS können die Behandlungsqualität steigern, jedoch gibt es noch keine ausreichende Evidenz eines Effekts auf funktionelle Langzeit-Outcomes. Darüber hinaus wurde gezeigt, dass ein strukturiertes Schulungsprogramm das Management von Delir, Sedierung und Analgesie auf der ITS verbessern kann. Neben strukturierten Schulungen kann auch eine komplexe telemedizinische Intervention in einem Netzwerk von ITS die Behandlungsqualität verbessern, gemessen an der Adhärenz zu evidenzbasierten Qualitätsindikatoren, die z.B. Weaning und Frühmobilisation betreffen. Zuletzt offenbarte eine systematische Netzwerkanalyse der PICS-Literatur, dass es zwar eine zunehmende Zahl an Studien zu PICS gibt, diese jedoch selten die Themen PICS-Prävention und PICS-Behandlung betreffen. Hier ergibt sich ein großer zukünftiger Forschungsbedarf, um PICS nicht nur zu erkennen, sondern auch effektiv zu verhindern und zu behandeln.

The Eastern Alps are subject to routine seismic monitoring by several national and regional agencies. However, the station density of the permanent local networks varies significantly, which has hindered the development of a high-resolution uniformly processed regional earthquake catalogue. The recent deployment of the temporary AlpArray Swath-D network has provided unparalleled station coverage for a two-year period, creating a unique opportunity for the detailed analysis of the seismicity of the Eastern Alps.

By utilising data from this network, I established a highly effective workflow for the detection, phase-picking, and localisation of low-magnitude seismicity using waveform based methods. This unique workflow yielded a high-resolution regional earthquake catalogue comprising 6,053 events and a completeness magnitude of ML -1.0. It is contingent on an efficient template matching code, which enabled me to integrate and expand upon existing earthquake catalogues from the well-established regional networks. Innovative picking methods were applied to automatically pick phase-arrivals based on a selection of manually picked events. These were then used to accurately localise the events within a recent local 3D velocity model. As a consequence of the high population density and industrialisation of the Eastern Alps, a considerable amount of anthropogenic signals are recorded continually in conjunction with the seismic events. I identified these signals with high confidence through the analysis of temporal signatures and satellite imagery. This is essential for an accurate interpretation of the spatial and temporal distribution of the earthquakes in the catalogue.

The obtained distribution of the earthquakes is largely consistent with known deformation patterns in the region observed through long-term seismic monitoring. A systematic variation of the b-values of the frequency-magnitude distribution indicates high differential stress in the area where previous GPS studies have identified the highest crustal deformation rates, and low differential stress in an area that is characterised by high uplift rates. To further expand the analysis of small-magnitude seismicity clusters, I applied techniques derived from graph theory. This enabled me to differentiate closely located earthquakes into sub-clusters associated with distinct faults. The relative relocalisation of events based on S-P differential travel-time inversion then allowed me to resolve the orientations of these faults, which exhibit a close correlation to fault plane solutions for moment tensor inversions of individual events within these sub-clusters.

The methodology that I present in this thesis has been demonstrated to be very effective for the detection of small earthquakes in low signal-to-noise recordings, resulting in an unprecedented image of the seismicity in the Eastern Alps over the two-year recording period of the AlpArray Swath-D network.

As the UN forecasts 68% of the world’s population will live in cities by 2050, understanding and addressing the mental and cognitive impacts of urban life is urgent. Studies consistently highlight nature’s positive effects on mood and cognition, contrasting with the negative influences of urban settings on brain function. However, the effect of perceived naturalness on brain and cognitive responses to environments remains underexplored. This dissertation investigates the behavioral and neural bases of naturalness perception through targeted experiments, aiming to enhance urban planning and architectural design. It includes four studies that examine how natural and built environments affect cognitive and psychological responses, each focusing on a different aspect of environmental influence on human behavior and brain activity. Article I investigated the neural and psychological mechanisms underlying the perception of naturalness versus artificiality in indoor architecture, utilizing functional Magnetic Resonance Imaging (fMRI) to map the neural correlates. Findings showed minimal influence of naturalness on subjective judgments but significant effects of lower-level visual features on perceived similarity. Neural analysis showed dissimilarities between natural and artificial interiors, mainly in the visual areas, highlighting the need for further investigation into the perception of architectural spaces and their neural correlates. Article II shifted focus to the domain of cognitive psychology, examining the differences in processing of visual symmetry and asymmetry within working memory (WM). The functional Near Infrared Spectroscopy (fNIRS) study investigated the effects of visual symmetry on working memory performance and neural responses, revealing that symmetry significantly enhances memory performance, particularly under high cognitive load conditions. Neuroimaging data showed distinct patterns of brain activation in response to symmetry, indicating complex, region-specific activation patterns within the brain that underscore the nuanced role of visual symmetry in cognitive processing. Article III found that the visibility and conditions of the sky significantly impact individuals’ selections of sky as an element of nature and their judgments of naturalness. The findings suggest complex interactions between environmental conditions, including horizon level and weather, in shaping perceptions of naturalness, underscoring the sky’s role in environmental psychology. Article IV further revealed that specific low-level visual features of the sky, such as fractal dimensions and brightness, significantly influence individuals’ perception of naturalness in environmental scenes. Key findings indicate that lower fractal dimensions and higher brightness of the sky enhance its selection as a natural element, impacting subjective evaluations of environmental naturalness. These results highlight the nuanced role of visual features in environmental psychology, offering insights into how the visual composition of the sky affects perceptions of natural environments. Together, these four publications contribute to a comprehensive understanding of the complex interplay between humans and naturalness of their environments, highlighting the important role of visual composition in this process.

Pflanzenkohle ist eine vielversprechende Negativemissionstechnologie (NET) und hat sich als vielseitiger Zuschlagstoff für Böden und Substrate als vorteilhaft erwiesen. Die Wirkung von Pflanzenkohlekompost und Pflanzenkohlesubstrate auf das Auswaschungsverhalten von Nähr- und Schadstoffen sowie auf die Wasserspeicherung in Böden wurde bisher nahezu nicht untersucht. Die vorliegende Dissertation setzt an dieser Stelle an und untersucht die Effekte von Pflanzenkohlen auf das Elutionsverhalten von Nähr- und Schadstoffen aus Komposten, Pflanzsubstraten und Böden im Bereich des Gartenbaus und der Landwirtschaft, auf Konversionsflächen sowie im urbanen Bereich der gemäßigten Klimazone. Proben- sowie methodenübergreifend (Schüttel- und Säulenperkolationsverfahren) betrachtet, führt die Co-Kompostierung von Pflanzenkohle i.d.R. zu einer Reduzierung der Nährstofffreisetzung sowohl aus frisch hergestellten als auch gealterten (gelagerten) Komposten. So wird die Auswaschung von Nitrat um 22 %, Phosphor um 20 %, Kalium um 5 %, Magnesium um 9 %, Calcium um 21 % und Schwefel um 2 % verringert. Im Falle von Nitrat, Phosphor und Magnesium zeigen 75 % der Materialien eine Verringerung der Auswaschung dieser Nährstoffe. Zudem konnte eine effektive Reduzierung des Torfeinsatzes durch die Anwendung pflanzenkohlebasierter spezifischer Pflanzsubstrate für Pflanzen verschiedener Klimazonen umgesetzt werden. Der in Parzellenversuchen untersuchte Effekt von Pflanzenkohle und Pflanzenkohlesubstrat-Einmischungen auf die Auswaschung aller 16 Einzel-PAK nach EPA ist vor allem bei den höhermolekularen PAK deutlich zu erkennen. Hier werden durchgängig Reduzierungen der PAK-Freisetzungen um bis zu 90 % gegenüber dem Kontrollboden beobachtet, oftmals sogar statistisch hochsignifikant. Im Tierpark Berlin-Friedrichsfelde angelegte Lysimeterversuche mit einer Versuchsdauer von 1.156 Tagen untersuchten den Effekt von Kompost, Pflanzenkohlekompost und Pflanzenkohle auf die Wasserspeicherung sowie das dynamische Freisetzungsverhalten von Makronährstoffen und Kupfer sowie Zink aus einem typischen bauschuttreichen urbanen Boden unter Freilandbedingungen. Die Zugabe von Kompost (mit/ohne Pflanzenkohle) führt zu einer signifikanten Verringerung der Sickerwassermengen, zu einer Erhöhung des pH-Wertes und der organischen Substanz sowie zu einer Verringerung der Rohdichte in den Lysimetern. Die Anwendung co-kompostierter Pflanzenkohle zeigt die besten Ergebnisse, alle ausgetragenen Frachten an Anionen und Kationen sowie der TOC-Austrag werden signifikant reduziert. Zusammenfassend kann hinsichtlich eines Einsparpotenzials von Gießwasser und Düngemittel, einer Reduzierung von Nährstoff- und PAK-Auswaschungen sowie einer Verringerung der Kupfer- und Zink-Frachten eindeutig die Anwendung von co-kompostierter Pflanzenkohle sowohl im Gartenbau, im urbanen Bereich als auch bei der Sanierung von kontaminierten Böden empfohlen werden. Das Zusammenwirken von organischem Material und co-kompostierter Pflanzenkohle zeigt die vielversprechendsten Ergebnisse hinsichtlich einer Steigerung des Umweltentlastungspotenzials durch die Reduzierung der Gefahr der Auswaschung von Nähr- und Schadstoffen in Richtung Grundwasser.

For both living organisms and artificial agents, exploration-exploitation decisions are ubiquitous and vital. They (co-)determine human behavior in all areas of life, from the smallest everyday decisions like grocery shopping to life-changing choices such as choice of a partner or a career. Understanding how exploration-exploitation decisions are made is therefore crucial to understanding – and potentially being able to influence – how and why humans behave the way they do. This dissertation contributes to exploration-exploitation research by examining behavioral, computational, neural, and physiological mechanisms behind exploration-exploitation decision-making. After a brief introduction in which I outline open questions and how this dissertation addresses them (Chapter 1), I proceed to investigate behavioral and computational signatures of exploring and exploiting (Chapter 2). To this end, I use a newly designed task which captures naturally paced exploration-exploitation behavior, while allowing participants to directly indicate whether they explore or exploit in a model-independent way. Having tested participants both in the lab and online, I demonstrate that this task reliably captures key behavioral characteristics of exploration-exploitation behavior and is well suited to its further use in combination with neurophysiological methods. Using computational modeling, I further probe the underlying decision-making processes and their relationship to behavior. The best-fitting computational model highlights different roles that reward and uncertainty estimates play in exploration and exploitation, as well as differences in how quickly acquired information about reward and uncertainty becomes obsolete. I then use the task and computational model presented in Chapter 2 to investigate neural (Chapter 3) and eye tracking (Chapter 4) mechanisms behind exploration-exploitation decision-making. In Chapter 3, I show that uncertainty-driven BOLD signal variability could function as a neural mechanism that allows to adapt exploration-exploitation behavior to a rapidly changing environment. In Chapter 4, I demonstrate that gaze patterns during the decision-making period predict the trial type (exploration or exploitation) and that patterns with different number of dwell locations provide complementary insights into the decision-making behind exploration-exploitation choices. Lastly, Chapter 5 provides a summary of contributions this dissertation makes to the field of exploration-exploitation research, discusses limitations and presents suggestions for future studies. All in all, this dissertation presents a comprehensive investigation of the underlying mechanisms of human exploration-exploitation behavior.